A Low-Cost, Integrated Immunization, Health, and Nutrition Intervention in Conflict Settings in Pakistan-The Impact on Zero-Dose Children and Polio Coverage.

Pakistan is one of two countries globally still endemic for poliovirus. While increasing immunization coverage is a concern, providing equitable access to care is also a priority, especially for conflict-affected populations. Recognizing these challenges, Naunehal, an integrated model of maternal, newborn, and child health (MNCH), immunization, and nutrition services delivered through community mobilization, mobile outreach, and private-sector engagement was implemented in conflict-affected union councils (UCs) with high poliovirus transmission, including Kharotabad 1(Quetta, Balochistan) and Bakhmal Ahmedzai (Lakki Marwat, Khyber Pakhtunkhwa). A quasi-experimental pre-post-design was used to assess the impact of the interventions implemented between April 2021 and April 2022, with a baseline and an endline survey. For each of the intervention UCs, a separate, matched-control UC was identified. At endline, the proportion of fully immunized children increased significantly from 27.5% to 51.0% in intervention UCs with a difference-in-difference (DiD) estimate of 13.6%. The proportion of zero-dose children and non-recipients of routine immunization (NR-RI) children decreased from 31.6% to 0.9% and from 31.9% to 3.4%, respectively, with a significant decrease in the latter group. Scaling up and assessing the adoption and feasibility of integrated interventions to improve immunization coverage can inform policymakers of the viability of such services in such contexts.

Quality improvement in public-private partnerships in low- and middle-income countries: a systematic review.

BACKGROUND: Public-private partnerships (PPP) are often how health improvement programs are implemented in low-and-middle-income countries (LMICs). We therefore aimed to systematically review the literature about the aim and impacts of quality improvement (QI) approaches in PPP in LMICs. METHODS: We searched SCOPUS and grey literature for studies published before March 2022. One reviewer screened abstracts and full-text studies for inclusion. The study characteristics, setting, design, outcomes, and lessons learned were abstracted using a standard tool and reviewed in detail by a second author. RESULTS: We identified 9,457 citations, of which 144 met the inclusion criteria and underwent full-text abstraction. We identified five key themes for successful QI projects in LMICs: 1) leadership support and alignment with overarching priorities, 2) local ownership and engagement of frontline teams, 3) shared authentic learning across teams, 4) resilience in managing external challenges, and 5) robust data and data visualization to track progress. We found great heterogeneity in QI tools, study designs, participants, and outcome measures. Most studies had diffuse aims and poor descriptions of the intervention components and their follow-up. Few papers formally reported on actual deployment of private-sector capital, and either provided insufficient information or did not follow the formal PPP model, which involves capital investment for a explicit return on investment. Few studies discussed the response to their findings and the organizational willingness to change. CONCLUSIONS: Many of the same factors that impact the success of QI in healthcare in high-income countries are relevant for PPP in LMICs. Vague descriptions of the structure and financial arrangements of the PPPs, and the roles of public and private entities made it difficult to draw meaningful conclusions about the impacts of the organizational governance on the outcomes of QI programs in LMICs. While we found many articles in the published literature on PPP-funded QI partnerships in LMICs, there is a dire need for research that more clearly describes the intervention details, implementation challenges, contextual factors, leadership and organizational structures. These details are needed to better align incentives to support the kinds of collaboration needed for guiding accountability in advancing global health. More ownership and power needs to be shifted to local leaders and researchers to improve research equity and sustainability.

Association of maternal, obstetric, fetal, and neonatal mortality outcomes with Lady Health Worker coverage from a cross-sectional survey of >10,000 households in Gilgit-Baltistan, Pakistan.

Pakistan has among the highest rates of maternal, perinatal, and neonatal mortality globally. Many of these deaths are potentially preventable with low-cost, scalable interventions delivered through community-based health worker programs to the most remote communities. We conducted a cross-sectional survey of 10,264 households during the baseline phase of a cluster randomized controlled trial (cRCT) in Gilgit-Baltistan, Pakistan from June-August 2021. The survey was conducted through a stratified, two-stage sampling design with the objective of estimating the neonatal mortality rate (NMR) within the study catchment area, and informing implementation of the cRCT. Study outcomes were self-reported and included neonatal death, stillbirth, health facility delivery, maternal death, postpartum hemorrhage (PPH), and Lady Health Worker (LHW) coverage. Summary statistics (proportions and rates) were weighted according to the sampling design, and mixed-effects Poisson regression was conducted to explore the relationship between LHW coverage and maternal/newborn outcomes. We identified 7,600 women who gave birth in the past five years, among whom 13% reported experiencing PPH. The maternal mortality ratio was 225 maternal deaths per 100,000 live births (95% confidence interval [CI] 137-369). Among 12,376 total births, the stillbirth rate was 41.4 per 1,000 births (95% CI 36.8-46.7) and the perinatal mortality rate was 53.0 per 1,000 births (95% CI 47.6-59.0). Among 11,863 live births, NMR was 16.2 per 1,000 live births (95% CI 13.6-19.3) and 65% were delivered at a health facility. LHW home visits were associated with declines in PPH (risk ratio [RR] 0.89 per each additional visit, 95% CI 0.83-0.96) and late neonatal mortality (RR 0.80, 95% CI 0.67-0.97). Intracluster correlation coefficients were also estimated to inform the planning of future trials. The high rates of maternal, perinatal, and neonatal death in Gilgit-Baltistan continue to fall behind targets of the 2030 Sustainable Development Goals.

Health trends in Canada 1990-2019: An analysis for the Global Burden of Disease Study.

OBJECTIVE: Monitoring trends in key population health indicators is important for informing health policies. The aim of this study was to examine population health trends in Canada over the past 30 years in relation to other countries. METHODS: We used data on disability-adjusted life years (DALYs), years of life lost (YLL), years lived with disability, life expectancy (LE), and child mortality for Canada and other countries between 1990 and 2019 provided by the Global Burden of Disease Study. RESULTS: Life expectancy, age-standardized YLL, and age-standardized DALYs all improved in Canada between 1990 and 2019, although the rate of improvement has leveled off since 2011. The top five causes of all-age DALYs in Canada in 2019 were neoplasms, cardiovascular diseases, musculoskeletal disorders, neurological disorders, and mental disorders. The greatest increases in all-age DALYs since 1990 were observed for substance use, diabetes and chronic kidney disease, and sense organ disorders. Age-standardized DALYs declined for most conditions, except for substance use, diabetes and chronic kidney disease, and musculoskeletal disorders, which increased by 94.6%, 14.6%, and 7.3% respectively since 1990. Canada's world ranking for age-standardized DALYs declined from 9th place in 1990 to 24th in 2019. CONCLUSION: Canadians are healthier today than in 1990, but progress has slowed in Canada in recent years in comparison with other high-income countries. The growing burden of substance abuse, diabetes/chronic kidney disease, and musculoskeletal diseases will require continued action to improve population health.

RéSUMé: OBJECTIF: La surveillance des tendances des indicateurs clés de la santé de la population est importante pour éclairer les politiques de santé. Dans cette étude, nous avons examiné les tendances de la santé de la population au Canada au cours des 30 dernières années par rapport à d'autres pays. MéTHODES: Nous avons utilisé des données sur les années de vie ajustées en fonction de l'incapacité (DALY), les années de vie perdues (YLL), les années vécues avec un handicap, l'espérance de vie (LE) et la mortalité infantile pour le Canada et d'autres pays entre 1990 et 2019, fournies par l'Étude mondiale sur le fardeau de la maladie. RéSULTATS: L'espérance de vie, les YLL ajustées selon l'âge et les DALY ajustées selon l'âge ont tous connu une amélioration au Canada entre 1990 et 2019, bien que le taux d'amélioration se soit stabilisé depuis 2011. Les cinq principales causes des DALY pour tous les âges au Canada en 2019 étaient les néoplasmes, les maladies cardiovasculaires, les affections musculosquelettiques, les affections neurologiques et les troubles mentaux. Les plus fortes augmentations des DALY pour tous les âges depuis 1990 ont été observées pour l'usage de substances, le diabète et les maladies rénales chroniques, ainsi que les troubles des organes sensoriels. Les DALY ajustées selon l'âge ont diminué pour la plupart des conditions, à l'exception de l'usage de substances, du diabète et des maladies rénales chroniques, ainsi que des troubles musculosquelettiques, qui ont augmenté de 94,6 %, 14,6 % et 7,3 % respectivement depuis 1990. Le classement mondial du Canada pour les DALY ajustées selon l'âge est diminué de la 9ième place en 1990 à la 24ième place en 2019. CONCLUSION: Les Canadiens sont en meilleure santé aujourd'hui qu'en 1990, mais les progrès se sont ralentis ces dernières années par rapport à d'autres pays à revenu élevé. La croissance du fardeau lié à l'abus de substances, au diabète/maladies rénales chroniques et aux affections musculosquelettiques exigera des actions continues pour améliorer la santé de la population.

Effect of Maternal and Newborn Care Service Package on Perinatal and Newborn Mortality: A Cluster Randomized Clinical Trial.

Importance: In resource-constrained settings where the neonatal mortality rate (NMR) is high due to preventable causes and health systems are underused, community-based interventions can increase newborn survival by improving health care practices. Objectives: To develop and evaluate the effectiveness of a community-based maternal and newborn care services package to reduce perinatal and neonatal mortality in rural Pakistan. Design, Setting, and Participants: This cluster randomized clinical trial was conducted between November 1, 2012, and December 31, 2013, in district Rahim Yar Khan in the province of Punjab. A cluster was defined as an administrative union council. Any consenting pregnant resident of the study area, regardless of gestational age, was enrolled. An ongoing pregnancy surveillance system identified 12 529 and 12 333 pregnancies in the intervention and control clusters, respectively; 9410 pregnancies were excluded from analysis due to continuation of pregnancy at the end of the study, loss to follow-up, or miscarriage. Participants were followed up until the 40th postpartum day. Statistical analysis was performed from January to May 2014. Intervention: A maternal and newborn health pack, training for community- and facility-based health care professionals, and community mobilization through counseling and education sessions. Main Outcomes and Measures: The primary outcome was perinatal mortality, defined as stillbirths per 1000 births and neonatal death within 7 days per 1000 live births. The secondary outcome was neonatal mortality, defined as death within 28 days of life per 1000 live births. Systematic random sampling was used to allocate 10 clusters each to intervention and control groups. Analysis was conducted on a modified intention-to-treat basis. Results: For the control group vs the intervention group, the total number of households was 33 188 vs 34 315, the median number of households per cluster was 3092 (IQR, 3018-3467) vs 3469 (IQR, 3019-4075), the total population was 229 155 vs 234 674, the mean (SD) number of residents per household was 6.9 (9.5) vs 6.8 (9.6), the number of males per 100 females (ie, the sex ratio) was 104.2 vs 103.7, and the mean (SD) number of children younger than 5 years per household was 1.0 (4.2) vs 1.0 (4.3). Altogether, 7598 births from conrol clusters and 8017 births from intervention clusters were analyzed. There was no significant difference in perinatal mortality between the intervention and control clusters (rate ratio, 0.86; 95% CI, 0.69-1.08; P = .19). The NMR was lower among the intervention than the control clusters (39.2/1000 live births vs 52.2/1000 live births; rate ratio, 0.75; 95% CI, 0.58-0.95; P = .02). The frequencies of antenatal visits and facility births were similar between the 2 groups. However, clean delivery practices were higher among intervention clusters than control clusters (63.2% [2284 of 3616] vs 13.2% [455 of 3458]; P < .001). Chlorhexidine use was also more common among intervention clusters than control clusters (55.9% [4271 of 7642] vs 0.3% [19 of 7203]; P < .001). Conclusions and Relevance: This pragmatic cluster randomized clinical trial demonstrated a reduction in NMR that occurred in the background of improved household intrapartum and newborn care practices. However, the effect of the intervention on antenatal visits, facility births, and perinatal mortality rates was inconclusive, highlighting areas requiring further research. Nevertheless, the improvement in NMR underscores the effectiveness of community-based programs in low-resource settings. Trial Registration: ClinicalTrials.gov Identifier: NCT01751945.

Preventing and Controlling Zinc Deficiency Across the Life Course: A Call to Action.

Through diverse roles, zinc determines a greater number of critical life functions than any other single micronutrient. Beyond the well-recognized importance of zinc for child growth and resistance to infections, zinc has numerous specific roles covering the regulation of glucose metabolism, and growing evidence links zinc deficiency with increased risk of diabetes and cardiometabolic disorders. Zinc nutriture is, thus, vitally important to health across the life course. Zinc deficiency is also one of the most common forms of micronutrient malnutrition globally. A clearer estimate of the burden of health disparity attributable to zinc deficiency in adulthood and later life emerges when accounting for its contribution to global elevated fasting blood glucose and related noncommunicable diseases (NCDs). Yet progress attenuating its prevalence has been limited due, in part, to the lack of sensitive and specific methods to assess human zinc status. This narrative review covers recent developments in our understanding of zinc's role in health, the impact of the changing climate and global context on zinc intake, novel functional biomarkers showing promise for monitoring population-level interventions, and solutions for improving population zinc intake. It aims to spur on implementation of evidence-based interventions for preventing and controlling zinc deficiency across the life course. Increasing zinc intake and combating global zinc deficiency requires context-specific strategies and a combination of complementary, evidence-based interventions, including supplementation, food fortification, and food and agricultural solutions such as biofortification, alongside efforts to improve zinc bioavailability. Enhancing dietary zinc content and bioavailability through zinc biofortification is an inclusive nutrition solution that can benefit the most vulnerable individuals and populations affected by inadequate diets to the greatest extent.

Pivoting school health and nutrition programmes during COVID-19 in low- and middle-income countries: A scoping review.

Background: Preventive and promotive interventions delivered by schools can support a healthy lifestyle, positive development, and well-being in children and adolescents. The coronavirus disease 2019 (COVID-19) pandemic presented unique challenges to school health and nutrition programmes due to closures and mobility restrictions. Methods: We conducted a scoping review to examine how school health and nutrition programmes pivoted during the COVID-19 pandemic, and to provide summative guidance to stakeholders in strategic immediate and long-term response efforts. We searched MEDLINE, Embase, PsycINFO, and grey literature sources for primary (observational, intervention, and programme evaluations) and secondary (reviews, best practices, and recommendations) studies conducted in low- and middle-income countries from January 2020 to June 2023. Programmes that originated in schools, which included children and adolescents (5-19.9 years) were eligible. Results: We included 23 studies in this review. They varied in their adaptation strategy and key programmatic focus, including access to school meals (n = 8), health services, such as immunisations, eye health, and water, sanitation, and hygiene-related activities (n = 4), physical activity curriculum and exercise training (n = 3), mental health counselling and curriculum (n = 3), or were multi-component in nature (n = 5). While school meals, physical activity, and mental health programmes were adapted by out-of-school administration (either in the community, households, or virtually), all health services were suspended indefinitely. Importantly, there was an overwhelming lack of quantitative data regarding modified programme coverage, utilisation, and the impact on children and adolescent health and nutrition. Conclusions: We found limited evidence of successful adaptation of school health and nutrition programme implementation during the pandemic, especially from Asia and Africa. While the adoption of the World Health Organization health-promoting school global standards and indicators is necessary at the national and school level, future research must prioritise the development of a school-based comprehensive monitoring and evaluation framework to track key indicators related to both health and nutrition of school-aged children and adolescents.

Association between the use of Accredited Social Health Activist (ASHA) services and uptake of institutional deliveries in India.

This study examines the impact of accredited social health activists (ASHAs), on increasing rates of institution-based deliveries among Indian women with a specific focus on the nine low-performing, empowered action group states and Assam (EAGA) in India. Using the latest round of the National Family Health Survey-V (2019-21), we first investigate the association between the use of ASHA services and socio-demographic attributes of women using a multivariate logistic regression. We then use propensity-score matching (PSM) to address observable selection bias in the data and assess the impact of ASHA services on the likelihood of institution-based deliveries using a generalized estimating equations model. Of the 232,920 women in our sample, 55.5% lived in EAGA states. Overall, 63.3% of women (70.6% in EAGA states) reported utilizing ASHA services, and 88.6% had an institution-based delivery (84.0% in EAGA states). Younger women from the poorest wealth index were more likely to use ASHA services and women in rural areas had a two-fold likelihood. Conversely, women with health insurance were less likely to use ASHA services compared to those without. Using PSM, the average treatment effect of using ASHA services on institution-based deliveries was 5.1% for all India (EAGA = 7.4%). The generalized estimating equations model indicated that the use of ASHA services significantly increased the likelihood of institution-based delivery by 1.6 times (95%CI = 1.5-1.7) for all India (EAGA = 1.8; 95%CI = 1.7-1.9). Our study finds that ASHAs are effective in enhancing the uptake of maternal services particularly institution-based deliveries. These findings underscore the necessity for continual, systematic investments to strengthen the ASHA program and to optimize the program's effectiveness in varied settings that rely on the community health worker model, thereby advancing child and maternal health outcomes.

An evidence gap map of interventions for noncommunicable diseases and risk factors among children and adolescents.

Substance misuse, obesity, mental health conditions, type 1 diabetes, cancers, and cardiovascular and chronic respiratory diseases together account for 41% of disability-adjusted life years linked to noncommunicable diseases (NCDs) among children and adolescents worldwide. However, the evidence on risk factors and interventions for this age group is scarce. Here we searched four databases to generate an evidence gap map of existing interventions and research gaps for these risk factors and NCDs. We mapped 159 reviews with 2,611 primary studies; most (96.2%) were conducted in high-income countries, and only 100 studies (3.8%) were from low- and middle-income countries (LMICs). The efficacy of therapeutic interventions on biomarkers and adverse events for NCDs appears to be well evidenced. Interventions for mental health conditions appear to be moderately evidenced, while interventions for obesity and substance misuse appear to be moderate to very low evidenced. Priority areas for future research include evaluating digital health platforms to support primary NCD prevention and management, and evaluating the impact of policy changes on the prevalence of obesity and substance misuse. Our findings highlight the wide disparity of evidence between high-income countries and LMICs. There is an urgent need for increased, targeted financing to address the research gaps in LMICs.

A Holistic Strategy of Mother and Child Health Care to Improve the Coverage of Routine and Polio Immunization in Pakistan: Results from a Demonstration Project.

BACKGROUND: The eradication of poliovirus and improving routine immunization (RI) coverage rates present significant challenges in Pakistan. There is a need for interventions that focus on strengthening community engagement to improve routine immunization coverage. Our primary objective is to assess the impact of an integrated strategy designed to enhance community engagement and maternal and child health immunization campaigns on immunization coverage in Pakistan's high-risk union councils of polio-endemic districts. METHOD: We implemented an integrated approach for routine immunization and maternal and child health in the polio-endemic district of Pakistan. This approach involved setting up health camps and actively engaging and mobilizing the local community. An independent team conducted surveys at three key points: baseline, midline, and endline, to evaluate immunization coverage among children under the age of five. The primary outcome measures for the study were coverage of OPV, IPV, and changes in the proportion of unvaccinated and fully vaccinated children. To select clusters and eligible households in each cluster, we utilized a 30 × 15 cluster sampling technique. Multivariable associations between socio-demographic factors and changes in the proportion of fully vaccinated children at the UC level were assessed using hierarchical linear regression models. RESULTS: A total of 256,946 children under the age of five (122,950 at baseline and 133,996 at endline) were enrolled in the study. By the endline, full immunization coverage had increased to 60% or more in all three study areas compared to the baseline. Additionally, there was a significant increase in the coverage of both OPV and IPV across all three provinces at the endline. The full immunization rates were assessed on three levels of the framework: the distal, intermediate (access and environment), and proximal level (camp attendance and effectiveness). At the distal level, on multivariate analysis, family size was found to be a significant predictor of change in immunity within the families (ß = 0.68; p ≤ 0.0001). At the intermediate level, the likelihood of full immunization decreased with the decrease in knowledge about vaccination (ß = -0.38; p = 0.002), knowledge about polio vaccine (ß = -0.25; p = 0.011), and knowledge about IPV (ß = -0.06; p = 0.546). Perceived obstacles to vaccination were fear of adverse events (ß = -0.4; p ≤ 0.0001) and lack of education (ß = 0.23; p = 0.031), which were found to be significant in bivariate and multivariate analyses. At the proximal level, community mobilization (ß = 0.26; p = 0.008) and attendance at health camp (ß = 0.21; p ≤ 0.0001) were found to enhance full immunization coverage. On the other hand, the most prominent reason for not attending health camp included no need to attend the health camp as the child was not ill (ß = -0.13; p = 0.008). CONCLUSIONS: This study found that community mobilization and attendance at health camps significantly enhanced full immunization coverage. The findings highlight the importance of community engagement and targeted interventions in improving immunization coverage and addressing barriers to healthcare seeking.

Young Adults' Hopes Regarding Noncommunicable Disease (NCD) Prevention and Management After the SARS-CoV-2 Virus Pandemic: Reflections From the NCD Child #YouthCOVIDCHAT Campaign.

PURPOSE: The SARS-CoV-2 virus pandemic has left a massive global death toll in its wake. Associated restrictions, precautions and lockdowns have disrupted daily routines, which has been associated with social isolation and major health implications for the world's youth. This paper shares young adults' visions for life beyond the pandemic as it relates to the prevention and management of noncommunicable diseases (NCDs). METHODS: NCD Child hosted a global Twitter campaign for young adults, some of whom are living with NCDs, to express their reflections on life beyond the pandemic. Contributions were subjected to qualitative thematic analysis. RESULTS: 52 responses from the campaign described six main themes: Health system strengthening; Access to care; Issues of sustainability, including the environment and the economy; Human rights, equity, and social issues; Mental health, and NCD prevention. DISCUSSION: Young adults expressed optimism about postpandemic life and emphasized the importance of comprehensive intersectoral approaches to create resilient health systems.

Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in Pakistan.

BACKGROUND: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). METHODS: HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell - IFN-γ activation was assessed by ELISpot. RESULTS: Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. CONCLUSIONS: Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.

An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.

BACKGROUND: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. METHODS: This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 µg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. DISCUSSION: This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. TRIAL REGISTRATION: NCT04798833, March 15, 2021.

Facility-Based Audit System With Integrated Community Engagement to Improve Maternal and Perinatal Health Outcomes in Rural Pakistan: Protocol for a Mixed Methods Implementation Study.

BACKGROUND: Maternal and newborn mortality in Pakistan remains as a major public health challenge. Pakistan faces significant infrastructure challenges and inadequate access to quality health care, exacerbated by sociocultural factors. Facility-based audit systems coupled with community engagement are key elements in achieving improved health system performance. We describe an implementation approach adapted from the World Health Organization audit cycle in real-world settings, with a plan to scale-up through mixed methods evaluation plan. OBJECTIVE: This study aims to implement a locally acceptable and relevant audit system and evaluate its feasibility within the rural health system of Pakistan for scale-up. METHODS: The implementation of the audit system comprises six phases: (1) identify facility and community leadership through consultative meetings with government district health offices, (2) establish the audit committee under the supervision of district health officer, (3) initiate audit with ongoing community engagement, (4) train the audit committee members, (5) launch the World Health Organization audit cycle (monthly meetings), and (6) quarterly review and refresher training. Data from all deliveries, live births, maternal deaths, maternal near misses, stillbirths, and neonatal deaths will be identified and recorded from four sources: (1) secondary-level care rural health facilities, (2) lady health workers' registers, (3) community representatives, and (4) project routine survey team. Concurrent quantitative and qualitative data will be drawn from case assessments, process analysis, and recommendations as components of iterative improvement cycles during the project. Outcomes will be the geographic distribution of mortality to measure the reach, proportion of facilities initiated to implement an audit system for measuring the adoption, proportion of audit committees with community representation, and proportion of audit committee members' sharing feedback regularly to measure acceptability and feasibility. In addition, outcomes of effectiveness will be measured based on data recording and reporting trends, identified modifiable factors for mortality and morbidity as underpinned by the Three Delays framework. Qualitative data will be analyzed based on perceived facilitators, barriers, and lessons learned for policy implications. Results will be summarized in frequencies and percentages and triangulated by the project team. Data will be analyzed using Stata (version 16; StataCorp) and NVivo (Lumivero) software. RESULTS: The study will be implemented for 20 months, followed by an additional 4-month period for follow-up. Initial results will be presented to the district health office and the District Health Program Management Team Meeting in the districts. CONCLUSIONS: This study will generate evidence about the feasibility and potential scale-up of a facility-based mortality audit system with integrated community engagement in rural Pakistan. Audit committees will complete the feedback loop linking health care providers, community representatives, and district health officials (policy makers). This implementation approach will serve decision makers in improving maternal and perinatal health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49578.

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

Probiotic Supplementation for Promotion of Growth in Undernourished Children: A Systematic Review and Meta-Analysis.

OBJECTIVES: Probiotic supplementation has been proposed as a therapeutic intervention to improve growth outcomes in children with undernutrition. The objective of this review is to synthesize the current evidence on probiotic supplementation for promotion of growth in undernourished children. METHODS: We searched MEDLINE, Cochrane CENTRAL, CINAHL, Embase, LILACS, and Scopus for randomized controlled trials (RCTs) that administered probiotics or eligible comparators to undernourished children below 5 years of age. Our primary outcomes of interest were weight-for-age, height-for-age, and weight-for-height at the longest follow-up points reported. Random-effects meta-analysis was used to calculate standardized mean differences (SMD) for continuous outcomes and risk ratios for dichotomous outcomes. The Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess certainty of the evidence. RESULTS: Nine RCTs with 5295 children in total were included. Durations of treatment ranged from 1 month to 1 year. Pooled analyses from 7 studies showed that probiotics may have little to no effect on weight-for-age (SMD 0.05 standard deviation [SD], 95% CI: -0.04 to 0.13, n = 2115 children; low-certainty evidence) and height-for-age (SMD -0.04 SD, 95% CI: -0.14 to 0.07, n = 1357 children; low-certainty evidence). The evidence was very uncertain about the effect on weight-for-height. CONCLUSIONS: Probiotics may have little to no effect on anthropometry in undernourished children, though there is considerable heterogeneity among the trials reviewed thus far. The interaction between gut microbiota and human nutrition is complex, and further research is needed to determine how the gut microbiome may contribute to undernutrition and how probiotics may affect growth in this vulnerable population.

Systematic Review of Management of Moderate Wasting in Children over 6 Months of Age.

The effective management of the 33 million children with moderate acute malnutrition (MAM) is key to reducing childhood morbidity and mortality. In this review, we aim to evaluate the effectiveness of specially formulated foods (SFFs) compared to non-food-based approaches to manage MAM in children >6 months old. We conducted a search on ten databases until 23 August 2021 and included five studies, covering 3387 participants. Meta-analysis of four studies comparing SFFs to counselling or standard of care showed that SFFs likely increase recovery rate, reduce non-response, and may improve weight-for-height z-score, weight-for-age z-score and time to recovery, but have little or no effect on MUAC gain. One study on a multicomponent intervention (SFFs, antibiotics and counselling provided to high-risk MAM) compared to counselling only was reported narratively. The intervention may increase weight gain after 24 weeks but may have little or no effect on weight gain after 12 weeks and on non-response and mortality after 12 and 24 weeks of enrollment. The effect of this intervention on recovery was uncertain. In conclusion, SFFs may be beneficial for children with moderate wasting in humanitarian contexts. Programmatic recommendations should consider context and cost-effectiveness.

Lessons from the development process of the Afghanistan integrated package of essential health services.

In 2017, in the middle of the armed conflict with the Taliban, the Ministry of Public Health decided that the Afghan health system needed a well-defined priority package of health services taking into account the increasing burden of non-communicable diseases and injuries and benefiting from the latest evidence published by DCP3. This leads to a 2-year process involving data analysis, modelling and national consultations, which produce this Integrated Package of Essential health Services (IPEHS). The IPEHS was finalised just before the takeover by the Taliban and could not be implemented. The Afghanistan experience has highlighted the need to address not only the content of a more comprehensive benefit package, but also its implementation and financing. The IPEHS could be used as a basis to help professionals and the new authorities to define their priorities.